Pathology of the Glomerulus Flashcards
What are podocytes?
They’re in the Bowman’s capsule in the kidneys and wrap around capillaries of the glomerulus - their foot process form the pedicels which aid in barrier to filtration of medium sized proteins
What substances are not filtered at the glomerulus?
All protein equal to or larger than albumin (including immunoglobulin) will NOT be filtered, they will stay in plasma
Describe the filtration barrier of the glomerulus
- Podocytes have interdigitating foot processes around the capillary
- Endothelial cell cytoplasm, basal lamina and podocyte
- Mesangial cells – modified smooth muscle cells and are continuous with vascular smooth muscle of arteriole; control blood flow through glomerulus
What is glomerulonephritis?
Term GN encompasses a number of conditions which:
• Are caused by pathology of glomerulus
• Present with proteinuria, Haematuria or both
• Diagnosed on renal biopsy
• Cause CKD
• Can progress to kidney failure (except minimal change disease)
What is the aetiology of glomerulonephritis?
- Immunoglobulin deposition
* No immunoglobulin deposition i.e. diabetic glomerular disease
What are the common presentations of glomerulonephritis?
- Haematuria (blood in urine)
- Heavy proteinuria (nephrotic syndrome)
- Slowly increasing proteinuria
- Acute renal failure
What are the for main causes of haematuria?
- UTI
- Urinary tract stone
- Urinary tract tumour
• Glomerulonephritis
What investigations are carried out for glomerulonephritis?
- Urine culture
- Ultrasound
- Check clotting then renal biopsy – shows accumulation of mesangial matrix (too many mesangial cells)
- Imummunohistochemistry
What are two immunohistochemistry tests for glomerulonephritis
- Immunoflourescence – immunoglobulin (of IgA type) and complement component C3 in mesangial area of all glomeruli
- Electron microscopy – deposits of IgA with prominent mesangial cells
Describe the pathology of IgA glomerulonephritis
Excess antibody (IgA) presents in serum, as it is stuck in the glomerulus in the mesagium and is not filtered into urine.
IgA stuck in mesagnial cells cause them to proliferate and produce more matrix, causing mesangial cell and matrix expansion
What is the prognosis of IgA nephropathy?
- Usually self-limiting
* Small % go onto chronic renal failure (continues deposition of matrix)
What are the investigations for IgA nephropathy?
Biopsy
• Thickening of glomerular filter
• New basement membrane under glomerular basement
Imunohistochemistry +ve for IgA deposits in matrix
• Basal lamina spike (matrix
What is the presentation of IgA glomerulonephritis?•
- Usually presents as nephritic
- Asymptomatic non-visible haematuria
- Increased BP
- Proteinuria <1g
Describe the pathophysiology of nephrotic syndrome
Filtration barrier is formed by Podocytes, glomerular basement membrane and endothelial cells.
Proteinuria results from podocyte pathology.
What is the presentation of nephrotic syndrome?
Generalised, pitting oedema
What is the triad of nephrotic syndrome?
Proteinuria >3g/24hr
Hypoalbuminaemia
Oedema
How does membranous glomerulonephritis arise?
Primary (idiopathic) or secondary to: • Malignancy • Infection (hep B/C, strep) • Immunological disease (sarcoidosis, rheumatoid arthritis) • Drugs (gold)
In some Pts, antigen phospholipase A2 receptor is present in idiopathic cases
What is the presentation of investigations of membranous glomerulonephritis?
• Distick proteinuria -> nephrotic syndrome (must be abnormal glomerular filer)
Check clotting screen and renal biopsy:
• Thickening glomerular basement membrane
• New basement membrane matrix under Podocytes
Electron microscopy
• Deposits of IgG
What is the pathophysiology of membranous glomerulonephritis?
IgG deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine
IgG activates complement (C3) which punch holes in filter
Leaky filter now allows albumin to be filtered into urine -> nephrotic syndrome
Describe the pathophysiology of diabetic nephropathy
Glycated molecules -> Matrix deposition in basal lamina underlying endothelium and in mesangial matrix -> thickened but leaky basement membranes + mesangial matrix compresses capillaries (no immune complexes)
Describe the changes that occur in diabetic nephropathy
- Small, compressed capillary lumen
- Adhesions to Bowmans capsule to try and prevent massive leakage of albumin into urine
- Thickening capillary wall which is leaking albumin
- Increase mesagnial matrix (which compresses capillaries)
- Thickened, arrow arterioles reduce blood flow to glomerulus
What are the clinical signs of diabetic nephropathy?
- Albuminuria
- Scarring (glomerulosclerosis)
- Nodule formation (Kimelsteil-Wilson Lesions) - gross excess of mesangial matrix
- Fibrosis
What is the prognosis of diabetic nephropathy?
Inevitable decline if 1. established diabetic nephropathy and if 2. continue poor diabetic control
What are the different patterns of injury in cresentric glomerulonephritis?
- Granulomatosis with polyangiitis (also known as Wegener’s granulomatosis)
- Microscopic polyarteritis (a disease very much like Wegeners)
- Antiglomerular basement membrane disease
What is Granulomatosis with polyangiitis (which can cause cresentric GN)?
A form of vasculitis (= inflammation in vessels) which affects vessels in kidneys, nose and lungs
What is a further test used for Wegener’s (which can cause cresenric GN)?
Serum test shows presence of anti-neutrophil cytoplasmic antibodies (ANCA)
How does cresentric GN present?
• Nephritic
Clotting and renal biopsy;
• Endothelial damage with fibrin deposition
• Cellular proliferation and influx of macrophages (forms a cresent) around glomerular tuft, with Bowman’s space
• Crushed glomerulus
What are anti-neutrophil cytoplasmic antibodies (ANCA)?
- Not deposited in kidney
- Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils
- Antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells
